Overlooked variations in calculating morphine equivalence raises questions of validity in epidemiology studies

Dasgupta, Nabarun; Wang, Manning; Kinlaw, Alan; Chidgey, Brooke; Cooper, Toska; Delcher, Chris

Overlooked variations in calculating morphine equivalence raises questions of validity in epidemiology studies

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September 30, 2022

Creator

Dasgupta, Nabarun
- Affiliation: Injury Prevention Research Center
Wang, Manning
- Other Affiliation: University of Florida
Kinlaw, Alan
- Affiliation: Eshelman School of Pharmacy
Chidgey, Brooke
- Affiliation: School of Medicine
Cooper, Toska
- Affiliation: Injury Prevention Research Center
Delcher, Chris
- Other Affiliation: University of Kentucky

Abstract

Background Morphine-standardized analgesic doses account for molecular potency. 90 milligrams of morphine equivalents (MME) per day are considered a “high dose” risk threshold. Although ubiquitously cited, the “CDC definition” of daily MME lacks a clearly defined denominator. Objectives Assess the sensitivity of denominator-dependency on “high dose” classification across 4 competing definitions. Methods Review of 27 studies cited in the CDC Pain Management Guideline yielded 4 unique definitions. Using Prescription Drug Monitoring Programs data (Jul-Sep 2018), we conducted a population-based cohort study of 3,916,461 patients receiving opioid analgesics in California (CA) and Florida (FL). The outcome was patients deemed “high dose” (>90 MME/day) across 4 definitions. Results In a simple example, a 30-day supply of 2 partially overlapping oxycodone prescriptions have daily MME varying across 4 definitions: 76mg (total days supply); 93mg (on-therapy days); 31mg (fixed observation window); or 105mg (maximum daily dose). Among 9,436,640 prescriptions, 42% overlapped, impacting daily MME. Across definitions, average daily MME varied 3-fold [range: 17-52 (CA), 23-65 mg (FL)]. Across definitions, prevalence of “high dose” individuals ranged 5.9%-14.2% (FL), 3.5%-10.3% (CA). Definitional variation would impact a hypothetical surveillance study trying to establish how much more “high dose” prescribing was present in FL than CA: from 34% to 79% more. Conclusions Previously unrecognized definitional variation confounds surveillance metrics and constrains real-world applicability of observational studies. While 90 MME may have cautionary mnemonic benefits, without harmonization of calculation, its utility is limited. Comparison between studies using daily MME requires explicit attention to definitional variation for validity.

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